Overdose Treatment. Naloxone is the drug of choice to treat methadone and other opioid overdose including heroin and morphine.
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5 Overdose Treatment Naloxone is the drug of choice to treat methadone and other opioid overdose including heroin and morphine. Specifically used to counteract lifethreatening depression of the CNS and respiratory system Extremely high affinity for μ-opioid receptor in the CNS. lib/emedicalexaminer/methadonepoisoning.ppt
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9 Heroin ( Junk, Smack, Horse") Heroin = diacetylmorphine Not a natural product More potent than morphine with a considerably stronger euphoric effect than morphine Its manufacture is legally prohibited (schedule I) Penetrates blood barrier faster than morphine (x 100) Metabolism: successive deacetylation Intermediate: monoacetylmorphine (MAM-6)
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31 Impact of Maintenance Treatment Reduction death rates (Grondblah, 90) Reduction IVDU (Ball & Ross, 91) Reduction crime days (Ball & Ross) Reduction rate of HIV seroconversion (Bourne, 88; Novick 90,; Metzger 93) Reduction relapse to IVDU (Ball & Ross) Improved employment, health, & social function
32 Methadone Methadone (Dolophine) 4,4-Diphenyl-6-dimethylamino- 3-heptanone Partial agonist Daily doses varies-depends on metabolism Satiates craving for heroin (in high enough doses), prevents withdrawal symptoms. "Dol" comes from the latin word "dolor" which means pain.
33 OTP Methadone AM = 120 mg 33
34 Mysteries Methadone-maintained patients are hypersensitive to pain, especially to cold pressor pain. Methadone-maintained patients are very tolerant to methadone & morphine analgesia Understanding-Medical-Issues.pps#449,4, Methadone Distribution* **
35 RESPONSE BY STIMULUS INTENSITY Controls Hyperalgesia: methadone maintenance Hyperalgesia/ Allodynia Pain Tolerance Response Pain Threshold Stimulus Intensity
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37 Methadone Single Dose Kinetics INTOXICATON T½ 5-6 hrs ANALGESIA T½ hrs PAIN Nilsson MI, et al. Acta anaesth. scand 1982, Suppl
38 Methadone for Pain Control 38
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40 ng/ml /3/2018
41 Methadone - USE IN PREGNANCY Pregnant women (SA) do better vs. untreated Advantages of methadone maintenance treatment during pregnancy include: longer gestational periods higher birth weights lower risk of fetal exposure to infectious diseases contracted through needle sharing West J Med January; 172(1): Medicine Cabinet Use of methadone Ilene B Anderson1 and Thomas E Kearney1 1 Department of Pharmacy, University of California, San Francisco, California Poison Control System, San Francisco Division, San Francisco General Hospital, Medical Center, 1001 Potrero Ave, Room 1E86, San Francisco, CA 94110
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43 Severity of Withdrawal Sxs Comparison of Spontaneous Withdrawals Heroin or Oxycontin Buprenorphine Methadone Days Since Last Dose Adapted from: Kosten, O Connor NEJM
44 Buprenorphine Buprenorphine (Buprenex, Subutex, Suboxone, Probuphine, Bunavail) 20 to 50 times more potent than morphine mu & kappa receptors - partial agonist delta receptors - antagonist Blocks the effects of high doses of heroin May precipitate withdrawal in highly addictive individuals 44
45 Buprenorphine Opioid Empty Receptor Receptor Sends Pain Signal to the Courtesy of NAABT, Brain Inc. (naabt.org) Withdrawal Pain Neuro receptor in withdrawal and craving opioids. Once dependent the body cannot produce enough natural opioids to satisfy the many new receptors that were produced while taking large doses of opioids over time. The unsatisfied receptor sends pain signals to the brain. This is withdrawal. 45
46 Perfect Fit - Maximum Opioid Effect Empty Receptor No Withdrawal Pain Courtesy of NAABT, Inc. (naabt.org) Euphoric Opioid Effect Neuro receptor satisfied with an opioid. The strong opioid effect from painkillers, or heroin, stops the withdrawal symptoms for a short time. (4-24 hours) The person is high. After prolonged use, the patient is no longer getting high so much as just preventing the withdrawal symptoms. 46
47 Courtesy of NAABT, Inc. (naabt.org) Imperfect Fit Limited Euphoric Opioid Effect Opioids replaced and blocked by Buprenorphine. Opioids cannot get to the neuro receptor while occupied by Buprenorphine. The person no longer feels sick (in withdrawal) and is unable to get high even if he/she uses other opioids. Buprenorphine produces a limited opioid effect, and cravings are reduced or eliminated. 47
48 Courtesy of NAABT, Inc. (naabt.org) Buprenorphine Still Blocks Opioids as It Dissipates Over time (24-72 hours) Buprenorphine dissipates, but still creates a small opioid effect (enough to prevent withdrawal) and still block opioids from attaching to the receptors. This means if someone were to take an opioid, they still would not get high. 48
49 Buprenorphine in pregnancy may be preferable to Methadone for pregnant women (Category B/C for both) Methadone is associated with improved birth outcomes in heroin-dependent mothers but the withdrawal for babies was "not trivial" In pregnant women on Buprenorphine, the babies withdraw within a few days and fewer require medical treatment
50 ~Bioavailability of Buprenorphine by route of administration Reprinted from Methadone Treatment for Opioid Dependence [Figure 13.2 (c)]. Strain, Eric C., M.D., and Maxine L. Stitzer, Ph.D., eds. The Johns Hopkins University Press. Baltimore, Maryland: The Johns Hopkins University Press, 1999: 300. Reprinted with permission from The Johns Hopkins University Press.
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